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Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide because of its high morbidity and the absence of effective therapies. Even though paclitaxel is a powerful anticancer chemotherapy drug, recent studies have indicated its ineffectiveness against GC cells. Long non-coding RNA (lncRNA) PVT1 has a high expression in GC cells and increases the progression of tumors via inducing drug resistance. In the present study, the effects of the siRNA-mediated lncRNA PVT1 gene silencing along with paclitaxel treatment on the rate of apoptosis, growth, and migration of AGS GC cells were investigated. AGS cells were cultured and then transfected with siRNA PVT1 using electroporation. The MTT test was used to examine the effect of treatments on the viability of cultured cells. Furthermore, the flow cytometry method was used to evaluate the impact of treatments on the cell cycle process and apoptosis induction in GC cells. Finally, the mRNA expression of target genes was assessed using the qRT-PCR method. The results showed that lncRNA PVT1 gene suppression, along with paclitaxel treatment, reduces the viability of cancer cells and significantly increases the apoptosis rate of cancer cells and the number of cells arrested in the G2/M phase compared to the control group. Based on the results of qRT-PCR, combined treatment significantly decreased the expression of MMP3, MMP9, MDR1, MRP1, Bcl-2, k-Ras, and c-Myc genes and increased the expression of the Bax gene compared to the control group. The results of our study showed that lncRNA PVT1 gene targeting, together with paclitaxel treatment, induces apoptosis, inhibits growth, alleviates drug resistance, and reduces the migratory capability of GC cells. Therefore, there is a need for further investigations to evaluate the feasibility and effectiveness of this approach in vivo in animal models.

Asunto(s)

Apoptosis , Resistencia a Antineoplásicos , Silenciador del Gen , Paclitaxel , ARN Largo no Codificante , Neoplasias Gástricas , ARN Largo no Codificante/genética , Paclitaxel/farmacología , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Apoptosis/genética , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , ARN Interferente Pequeño/genética

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With the aim of diversifying different energy sources and achieving net zero emissions, hybrid renewable energy sources (HRES) represent the future of the world. However, several HRES simulation software do not integrate the Photovoltaic/thermal (PV/T) system. This article designs an optimal design model for a tri-hybrid Photovoltaic/thermal/hydroelectric (PV/T/H) system for a rural locality in the North Cameroon region. The two Demand Side Management (DSM) strategies used reveal that the DSM strategy significantly reduced the energy cost by 59 % and the emission by CO 2 22 % compared to the No-DSM mode. Although the use of battery storage (BSS) is used in both cases, the optimal solutions obtained thanks to the multi-objective optimization method implemented on Matlab led to 418 PV/T panels, 2 MH generators, 2 diesel generators (DG) and 217 PV/T panels and 1 DG for DSM and No-DSM mode respectively. This study is a demonstration of the effect of dynamic tariffs and active demand management technologies on PV/T/H modeling and optimization. It also reveals the need to hybridize PV/T with other energy systems to increase performance and achieve net zero emissions.

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INTRODUCTION: Human oral squamous cell carcinoma (OSCC) is the most common type of oral cancer and has a poor survival rate. Cell-cell communication between OSCC cells and cancer-associated fibroblasts (CAFs) plays important roles in OSCC progression. We previously demonstrated that CAFs promote OSCC cell migration and invasion. However, how OSCC cells influence CAFs proliferation is unknown. METHODS: Knockdown of PVT1 was confirmed using lentivirus infection technique. CAFs in tissues were identified by staining the cells with α-SMA using immunohistochemical technique. CCK-8 assay was used to evaluate cell proliferation. The mRNA level of a gene was measured by qRT-PCR. Secreted TGF-ß were detected using ELISA assay. RESULTS: We found that knockdown of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was associated with a low density of CAFs in xenograft tumors in mice; further analysis revealed that PVT1 in OSCC cells induced CAF proliferation through transforming growth factor (TGF)-ß. DISCUSSION: Our results demonstrate that lncRNA PVT1 in tumor cells participates in CAF development in OSCC by regulating TGF-ß. This study revealed a new mechanism by which PVT1 regulates OSCC progression and PVT1 is a potential therapeutic target in OSCC.

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To establish ubiquitous and energy-efficient wireless sensor networks (WSNs), short-range Internet of Things (IoT) devices require Bluetooth low energy (BLE) technology, which functions at 2.4 GHz. This study presents a novel approach as follows: a fully integrated all-digital phase-locked loop (ADPLL)-based Gaussian frequency shift keying (GFSK) modulator incorporating two-point modulation (TPM). The modulator aims to enhance the efficiency of BLE communication in these networks. The design includes a time-to-digital converter (TDC) with the following three key features to improve linearity and time resolution: fast settling time, low dropout regulators (LDOs) that adapt to process, voltage, and temperature (PVT) variations, and interpolation assisted by an analog-to-digital converter (ADC). It features a digital controlled oscillator (DCO) with two key enhancements as follows: ΔΣ modulator dithering and hierarchical capacitive banks, which expand the frequency tuning range and improve linearity, and an integrated, fast-converging least-mean-square (LMS) algorithm for DCO gain calibration, which ensures compliance with BLE 5.0 stable modulation index (SMI) requirements. Implemented in a 28 nm CMOS process, occupying an active area of 0.33 mm2, the modulator demonstrates a wide frequency tuning range of from 2.21 to 2.58 GHz, in-band phase noise of -102.1 dBc/Hz, and FSK error of 1.42% while consuming 1.6 mW.

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Cardiac fibrosis is a commonly seen pathophysiological process in various cardiovascular disorders, such as coronary heart disorder, hypertension, and cardiomyopathy. Cardiac fibroblast trans-differentiation into myofibroblasts (MFs) is a key link in myocardial fibrosis. LncRNA PVT1 participates in fibrotic diseases in multiple organs; however, its role and mechanism in cardiac fibrosis remain largely unknown. Human cardiac fibroblasts (HCFs) were stimulated with TGF-ß1 to induce myofibroblast; Immunofluorescent staining, Immunoblotting, and fluorescence in situ hybridization were used to detect the myofibroblasts phenotypes and lnc PVT1 expression. Cell biological phenotypes induced by lnc PVT1 knockdown or overexpression were detected by CCK-8, flow cytometry, and Immunoblotting. A mouse model of myocardial fibrosis was induced using isoproterenol (ISO), and the cardiac functions were examined by echocardiography measurements, cardiac tissues by H&E, and Masson trichrome staining. In this study, TGF-ß1 induced HCF transformation into myofibroblasts, as manifested as significantly increased levels of α-SMA, vimentin, collagen I, and collagen III; the expression level of lnc PVT1 expression showed to be significantly increased by TGF-ß1 stimulation. The protein levels of TGF-ß1, TGFBR1, and TGFBR2 were also decreased by lnc PVT1 knockdown. Under TGF-ß1 stimulation, lnc PVT1 knockdown decreased FN1, α-SMA, collagen I, and collagen III protein contents, inhibited HCF cell viability and enhanced cell apoptosis, and inhibited Smad2/3 phosphorylation. Lnc PVT1 positively regulated MYC expression with or without TGF-ß1 stimulation; MYC overexpression in TGF-ß1-stimulated HCFs significantly attenuated the effects of lnc PVT1 knockdown on HCF proliferation and trans-differentiation to MFs. In the ISO-induced myocardial fibrosis model, lnc PVT1 knockdown partially reduced fibrotic area, improved cardiac functions, and decreased the levels of fibrotic markers. In addition, lnc PVT1 knockdown decreased MYC and CDK4 levels but increased E-cadherin in mice heart tissues. lnc PVT1 is up-regulated in cardiac fibrosis and TGF-ß1-stimulated HCFs. Lnc PVT1 knockdown partially ameliorates TGF-ß1-induced HCF activation and trans-differentiation into MFs in vitro and ISO-induced myocardial fibrosis in vivo, potentially through interacting with MYC and up-regulating MYC.

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BACKGROUND: Cirrhosis causes an imbalance in the coagulation pathway and leads to a tendency for both bleeding and clotting. SARS-CoV-2 has been reported to be associated with a hypercoagulable state. This study examines SARS-CoV-2's impact on hemostasis in compensated patients with cirrhosis. METHODS: We analyzed the US Collaborative Network, which comprises 63 HCOs in the U.S.A. Compensated cirrhosis patients were split into two groups: SARS-CoV-2-positive and -negative. Patients' baseline characteristics were used in a 1:1 propensity score-matched module to create comparable cohorts. We compared the risk of portal vein thrombosis (PVT), deep venous thrombosis (DVT), and pulmonary embolism (PE) at 6 months, and 1 and 3 years. RESULTS: Of 330,521 patients, 27% tested positive and 73% remained negative. After PSM, both cohorts included 74,738 patients. Patients with SARS-CoV-2 had a higher rate of PVT compared to those without at 6 months (0.63% vs 0.5%, p < 0.05), 1 year (0.8% vs 0.6%, p < 0.05), and 3 years (1% vs. 0.7%, p < 0.05), a higher rate of DVT at 6 months (0.8% vs. 0.4%, p < 0.05), 1 year (1% vs. 0.5%, p < 0.05), and 3 years (1.4% vs. 0.8%, p < 0.05), and a higher rate of PE at 6 months (0.6% vs. 0.3%, p < 0.05), 1 year (0.7% vs. 0.4%, p < 0.05), and 3 years (1% vs. 0.6%, p < 0.05). CONCLUSIONS: The presence of SARS-CoV-2 infection in patients with compensated cirrhosis was associated with a higher rate of PVT, DVT, and PE at 6 months, and 1 and 3 years.

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BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common type of blood cancer in children. Aberrant expression of long noncoding RNAs (lncRNAs) may set stages for ALL development. LncRNAs are emerging as a novel diagnostic and prognostic biomarker for ALL. Herein, we aimed to evaluate the expression of lncRNA GJA9-MYCBP and PVT1 in blood samples of ALL and healthy individuals. METHODS: As a case-control study, 40 pairs of ALL and healthy individual samples were used. The expression of MYC and each candidate lncRNA was measured using quantitative real-time PCR. Any possible association between the expression of putative noncoding RNAs and clinicopathological characteristics was also evaluated. RESULTS: LncRNA GJA9-MYCBP and PVT1 were significantly upregulated in ALL samples compared with healthy ones. Similarly, mRNA levels of MYC were increased in ALL samples than control ones. Receiver operating characteristic curve analysis indicated a satisfactory diagnostic efficacy (p-value <.0001), suggesting that lncRNA GJA9-MYCBP and PVT1 may serve as a diagnostic biomarker for ALL. Linear regression analysis unveiled positive correlations between the expression level of MYC and lncRNA GJA9-MYCBP and PVT1 in ALL patients (p-values <.01). CONCLUSIONS: In this study, we provided approval for the clinical diagnostic significance of lncRNA GJA9-MYCBP and PVT1that their upregulations may be a diagnostic biomarker for ALL.

Asunto(s)

Biomarcadores de Tumor , Leucemia-Linfoma Linfoblástico de Células Precursoras , ARN Largo no Codificante , Regulación hacia Arriba , Humanos , ARN Largo no Codificante/genética , Biomarcadores de Tumor/genética , Masculino , Femenino , Estudios de Casos y Controles , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Niño , Pronóstico , Preescolar , Adolescente , Curva ROC , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo

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Background and aims: Management of severe thrombocytopenia poses significant challenges in patients with chronic liver disease. Here, we aimed to evaluate the first real-world European post-marketing cohort of cirrhotic patients treated with lusutrombopag, a thrombopoietin receptor agonist, verifying the efficacy and safety of the drug. Methods: In the REAl-world Lusutrombopag treatment in ITalY (REALITY) study, we collected data from consecutive cirrhotic patients treated with lusutrombopag in 19 Italian hepatology centers, mostly joined to the "Club Epatologi Ospedalieri" (CLEO). Primary and secondary efficacy endpoints were the ability of lusutrombopag to avoid platelet transfusions and to raise the platelet count to ≥50,000/µL, respectively. Treatment-associated adverse events were also collected. Results: A total of 66 patients and 73 cycles of treatment were included in the study, since 5 patients received multiple doses of lusutrombopag over time for different invasive procedures. Fourteen patients (19%) had a history of portal vein thrombosis (PVT). Lusutrombopag determined a significant increase in platelet count [from 37,000 (33,000-44,000/µL) to 58,000 (49,000-82,000), p < 0.001]. The primary endpoint was met in 84% of patients and the secondary endpoint in 74% of patients. Baseline platelet count was the only independent factor associated with response in multivariate logistic regression analysis (OR for any 1000 uL of 1.13, CI95% 1.04-1.26, p 0.01), with a good discrimination power (AUROC: 0.78). Notably, a baseline platelet count ≤ 29,000/µL was identified as the threshold for identifying patients unlikely to respond to the drug (sensitivity of 91%). Finally, de novo PVT was observed in four patients (5%), none of whom had undergone repeated treatment, and no other safety or hemorrhagic events were recorded in the entire population analyzed. Conclusions: In this first European real-world series, lusutrombopag demonstrated efficacy and safety consistent with the results of registrational studies. According to our results, patients with baseline platelet counts ≤29,000/µL are unlikely to respond to the drug.

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The accurate estimation of gas viscosity remains a pivotal concern for petroleum engineers, exerting substantial influence on the modeling efficacy of natural gas operations. Due to their time-consuming and costly nature, experimental measurements of gas viscosity are challenging. Data-based machine learning (ML) techniques afford a resourceful and less exhausting substitution, aiding research and industry at gas modeling that is incredible to reach in the laboratory. Statistical approaches were used to analyze the experimental data before applying machine learning. Seven machine learning techniques specifically Linear Regression, random forest (RF), decision trees, gradient boosting, K-nearest neighbors, Nu support vector regression (NuSVR), and artificial neural network (ANN) were applied for the prediction of methane (CH4), nitrogen (N2), and natural gas mixture viscosities. More than 4304 datasets from real experimental data utilizing pressure, temperature, and gas density were employed for developing ML models. Furthermore, three novel correlations have developed for the viscosity of CH4, N2, and composite gas using ANN. Results revealed that models and anticipated correlations predicted methane, nitrogen, and natural gas mixture viscosities with high precision. Results designated that the ANN, RF, and gradient Boosting models have performed better with a coefficient of determination (R2) of 0.99 for testing data sets of methane, nitrogen, and natural gas mixture viscosities. However, linear regression and NuSVR have performed poorly with a coefficient of determination (R2) of 0.07 and - 0.01 respectively for testing data sets of nitrogen viscosity. Such machine learning models offer the industry and research a cost-effective and fast tool for accurately approximating the viscosities of methane, nitrogen, and gas mixture under normal and harsh conditions.

RESUMEN

BACKGROUND: Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant translocation 1 (PVT1), have emerged as significant regulators of OS metastasis. Recent studies have indicated that activation of signal transducer and activator of transcription 3 (STAT3) signaling, which might be controlled by PVT1, inhibits ferroptosis to promote the malignant progression of cancer. Therefore, the present study aimed to determine the role of PVT1 in OS pathogenesis and investigate whether PVT1 affects OS progression by regulating STAT3/GPX4 pathway-mediated ferroptosis. METHODS: The human OS cell line MG63 were transfected with sh-PVT1 plasmid to inhibit PVT1 expression, with or without co-transfection with a STAT3 overexpression plasmid. The expression of PVT1 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion, and apoptosis of MG63 cells were determined using the cell counting kit-8 (CCK8), Transwell assay, and flow cytometry. The levels of malondialdehyde (MDA), Fe2+, and glutathione (GSH) were determined by ELISA kits, whereas reactive oxygen species (ROS) level was determined by immunofluorescence. The protein expression levels of STAT3, p-STAT3, and glutathione peroxidase 4 (GPX4) were detected by western blot (WB). RESULTS: PVT1 expression was significantly increased in MG63 cells. When knocking down PVT1 with sh-PVT1 plasmid, the proliferation, migration, and invasion of MG63 cells were markedly inhibited, while the rate of apoptosis was upregulated. Further investigation revealed that MG63 cells with PVT1 knockdown exhibited elevated levels of MDA, Fe2+, and ROS. In addition, the inhibition of PVT1 expression resulted in decreased levels of GSH and inhibited expression of p-STAT3 and GPX4. When sh-PVT1 was co-transfected with STAT3 overexpression plasmid in MG63 cells, the increased levels of MDA, Fe2+, and ROS were downregulated, and the decreased expressions of GSH, p-STAT3, and GPX4 were upregulated. CONCLUSION: PVT1 promotes OS metastasis by activating the STAT3/GPX4 pathway to inhibit ferroptosis. Targeting PVT1 might be a novel therapeutic strategy for OS treatment.

Asunto(s)

Neoplasias Óseas , Ferroptosis , Osteosarcoma , ARN Largo no Codificante , Humanos , Apoptosis/genética , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Osteosarcoma/genética , Osteosarcoma/metabolismo , Osteosarcoma/patología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Especies Reactivas de Oxígeno/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transducción de Señal , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética

RESUMEN

Nowadays, the long-life management of patients with aortic stenosis has emerged as one of the most debated issues. Transcatheter aortic valve replacement is more frequently performed in younger patients with lower surgical risk, and also the number of valve-in-valve (ViV) procedures has increased in the last few years. However, coronary obstruction is the most dreadful complication related to this procedure. To prevent coronary obstruction in the context of transcatheter aortic ViV implantation, the BASILICA (bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction) technique was developed. Although effective, BASILICA is complex and time-consuming. Hence, simpler, reproducible, and faster strategies are desirable. Here we present a promising simplified BASILICA technique employing an Armada Balloon to perform the leaflet laceration.

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Estenosis de la Válvula Aórtica , Válvula Aórtica , Prótesis Valvulares Cardíacas , Diseño de Prótesis , Humanos , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/fisiopatología , Resultado del Tratamiento , Válvula Aórtica/cirugía , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/instrumentación , Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Enfermedad Iatrogénica

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Long noncoding RNA (lncRNA) is involved in many malignant tumors. This study aimed to clarify the role of the lncRNA plasmacytoma variant translocation 1 (PVT1) in CRC growth and metastasis. METHODS: Differentially expressed lncRNAs in CRC were analyzed using the Cancer Genome Atlas. Gene expression profiling interactive analysis and a comprehensive resource for lncRNAs from cancer arrays databases were used to analyze lncRNA PVT1 expression and CRC prognosis, respectively. Cell counting kit-8, wound healing, colony formation, Transwell, and immunofluorescence assays were used to evaluate CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), respectively. Tumor growth and metastasis models were used to explore the PVT1 effect on the growth and metastasis of CRC in vivo. RESULTS: PVT1 was highly expressed in CRC, associated with a poor prognosis of CRC, and showed good diagnostic value. Transfection of sh-PVT1 or pcDNA3.1-PVT1 reduced or increased the proliferation, wound healing rate, colony formation, invasion, and EMT of CRC cells. PVT1 and miR-3619-5p were co-expressed in CRC cytoplasm, and PVT1 acted as a competitive endogenous RNA (ceRNA) by sponging miR-3619-5p to up-regulate tripartite motif containing 29 (TRIM29) expression. MiR-3619-5p overexpression and TRIM29 knockdown reduced proliferation, wound healing rate, invasion, and EMT of CRC cells. However, simultaneous PVT1 and miR-3619-5p overexpression or knockdown of miR-3619-5p and TRIM29 knockdown rescued the malignant phenotype of CRC cells. CONCLUSIONS: We first clarified the ceRNA mechanism of PVT1 in CRC, which induced growth and metastasis by sponging with miR-3619-5p to regulate TRIM29.

Asunto(s)

Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , MicroARNs , ARN Largo no Codificante , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , ARN Largo no Codificante/genética , MicroARNs/genética , Proliferación Celular/genética , Ratones , Animales , Pronóstico , Transición Epitelial-Mesenquimal/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Masculino , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Ratones Desnudos , Femenino , Línea Celular Tumoral , Metástasis de la Neoplasia , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

AIMS: Ablation of monomorphic ventricular tachycardia (MMVT) has been shown to reduce shock frequency and improve survival. We aimed to compare cause-specific risk factors for MMVT and polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF) and to develop predictive models. METHODS AND RESULTS: The multicentre retrospective cohort study included 2668 patients (age 63.1 ± 13.0 years; 23% female; 78% white; 43% non-ischaemic cardiomyopathy; left ventricular ejection fraction 28.2 ± 11.1%). Cox models were adjusted for demographic characteristics, heart failure severity and treatment, device programming, and electrocardiogram metrics. Global electrical heterogeneity was measured by spatial QRS-T angle (QRSTa), spatial ventricular gradient elevation (SVGel), azimuth, magnitude (SVGmag), and sum absolute QRST integral (SAIQRST). We compared the out-of-sample performance of the lasso and elastic net for Cox proportional hazards and the Fine-Gray competing risk model. During a median follow-up of 4 years, 359 patients experienced their first sustained MMVT with appropriate implantable cardioverter-defibrillator (ICD) therapy, and 129 patients had their first PVT/VF with appropriate ICD shock. The risk of MMVT was associated with wider QRSTa [hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.01-1.34], larger SVGel (HR 1.17; 95% CI 1.05-1.30), and smaller SVGmag (HR 0.74; 95% CI 0.63-0.86) and SAIQRST (HR 0.84; 95% CI 0.71-0.99). The best-performing 3-year competing risk Fine-Gray model for MMVT [time-dependent area under the receiver operating characteristic curve (ROC(t)AUC) 0.728; 95% CI 0.668-0.788] identified high-risk (> 50%) patients with 75% sensitivity and 65% specificity, and PVT/VF prediction model had ROC(t)AUC 0.915 (95% CI 0.868-0.962), both satisfactory calibration. CONCLUSION: We developed and validated models to predict the competing risks of MMVT or PVT/VF that could inform procedural planning and future randomized controlled trials of prophylactic ventricular tachycardia ablation. CLINICAL TRIAL REGISTRATION: URL:www.clinicaltrials.gov Unique identifier:NCT03210883.

Asunto(s)

Desfibriladores Implantables , Prevención Primaria , Taquicardia Ventricular , Fibrilación Ventricular , Humanos , Femenino , Masculino , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/prevención & control , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/terapia , Persona de Mediana Edad , Estudios Retrospectivos , Prevención Primaria/métodos , Factores de Riesgo , Medición de Riesgo , Anciano , Fibrilación Ventricular/prevención & control , Fibrilación Ventricular/diagnóstico , Fibrilación Ventricular/fisiopatología , Fibrilación Ventricular/terapia , Resultado del Tratamiento , Cardioversión Eléctrica/instrumentación , Cardioversión Eléctrica/efectos adversos , Electrocardiografía , Ablación por Catéter , Factores de Tiempo , Muerte Súbita Cardíaca/prevención & control , Muerte Súbita Cardíaca/etiología

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PURPOSE: The present prospective cohort study was intended to present the minimum 3 years' results of flexible posterior vertebral tethering (PVT) applied to 10 skeletally immature patients with SK to question, if it could be an alternative to fusion. METHODS: Ten skeletally immature patients with radiographically confirmed SK, who had flexible (minimum 35%) kyphotic curves (T2-T12), were included. A decision to proceed with PVT was based on curve progression within the brace, and/or persistent pain, and/or unacceptable cosmetic concerns of the patient/caregivers, and/or non-compliance within the brace. RESULTS: Patients had an average age of 13.1 (range 11-15) and an average follow-up duration of 47.6 months (range 36-60). Posterior vertebral tethering (PVT) was undertaken to all patients by utilizing Wiltse approach and placing monoaxial pedicle screws intermittently. At the final follow-up: mean pre-operative thoracic kyphosis and lumbar lordosis improved from 73.6°-45.7° to 34.7°-32.1°. Mean sagittal vertical axis, vertebral wedge angle and total SRS-22 scores improved significantly. A fulcrum lateral X-ray obtained at the latest follow-up, showed that the tethered levels remained mobile. CONCLUSION: This study, for the first time in the literature, concluded, that as a result of growth modulation applied to skeletally immature patients with SK, flexible PVT was detected to yield gradual correction of the thoracic kyphosis by reverting the pathological vertebral wedging process, while keeping the mobility of the tethered segments in addition to successful clinical-functional results. The successful results of the present study answered the role of the PVT as a viable alternative to fusion in skeletally immature patients with SK. LEVEL OF EVIDENCE: IV.

Asunto(s)

Enfermedad de Scheuermann , Humanos , Niño , Femenino , Masculino , Adolescente , Enfermedad de Scheuermann/cirugía , Enfermedad de Scheuermann/diagnóstico por imagen , Resultado del Tratamiento , Estudios de Seguimiento , Radiografía/métodos , Estudios Prospectivos , Vértebras Torácicas/cirugía , Vértebras Torácicas/diagnóstico por imagen , Cifosis/cirugía , Cifosis/diagnóstico por imagen , Fusión Vertebral/métodos , Vértebras Lumbares/cirugía , Vértebras Lumbares/diagnóstico por imagen

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Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14-16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood.

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BACKGROUND: Cerebral cavernous malformation (CCM) is a low-flow, bleeding-prone vascular disease that can cause cerebral hemorrhage, seizure and neurological deficits. Its inheritance mode includes sporadic or autosomal dominant inheritance with incomplete penetrance, namely sporadic CCM (SCCM) and familial CCM. SCCM is featured by single lesion and single affection in a family. Among CCM patients especially SCCM, the pathogenesis of the corresponding phenotypes and pathological features or candidate genes have not been fully elucidated yet. METHODS: Here, we performed in-depth single-cell RNA sequencing (scRNA-Seq) and bulk assay for transposase-accessible chromatin sequencing (ATAC-Seq) in SCCM and control patients. Further validation was conducted for the gene of interest using qPCR and RNA in situ hybridization (RNA FISH) techniques to provide further atlas and evidence for SCCM generative process. RESULTS: We identified six cell types in the SCCM and control vessels and found that the expression of NEK1, RNPC3, FBRSL1, IQGAP2, MCUB, AP3B1, ESCO1, MYO9B and PVT1 were up-regulated in SCCM tissues. Among the six cell types, we found that compared with control conditions, PVT1 showed a rising peak which followed the pseudo-time axis in endothelial cell clusters of SCCM samples, while showed an increasing trend in smooth muscle cell clusters of SCCM samples. Further experiments indicated that, compared with the control vessels, PVT1 exhibited significantly elevated expression in SCCM samples. CONCLUSION: In SCCM conditions, We found that in the process of development from control to lesion conditions, PVT1 showed a rising peak in endothelial cells and showed an increasing trend in smooth muscle cells at the same time. Overall, there was a significantly elevated expression of NEK1, RNPC3, FBRSL1, IQGAP2, MCUB, AP3B1, ESCO1, MYO9B and PVT1 in SCCM specimens compared to control samples.

Asunto(s)

Hemangioma Cavernoso del Sistema Nervioso Central , Análisis de la Célula Individual , Humanos , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Análisis de la Célula Individual/métodos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Células Endoteliales/metabolismo , Células Endoteliales/patología

RESUMEN

Super-enhancers are unique gene expression regulators widely involved in cancer development. Spread over large DNA segments, they tend to be found next to oncogenes. The super-enhancer c-MYC locus forms long-range chromatin looping with nearby genes, which brings the enhancer and the genes into proximity, to promote gene activation. The colon cancer-associated transcript 1 (CCAT1) gene, which is part of the MYC locus, transcribes a lncRNA that is overexpressed in colon cancer cells through activation by MYC. Comparing different types of cancer cell lines using RNA fluorescence in situ hybridization (RNA FISH), we detected very prominent CCAT1 expression in HeLa cells, observed as several large CCAT1 nuclear foci. We found that dozens of CCAT1 transcripts accumulate on the gene locus, in addition to active transcription occurring from the gene. The accumulating transcripts are released from the chromatin during cell division. Examination of CCAT1 lncRNA expression patterns on the single-RNA level showed that unspliced CCAT1 transcripts are released from the gene into the nucleoplasm. Most of these unspliced transcripts were observed in proximity to the active gene but were not associated with nuclear speckles in which unspliced RNAs usually accumulate. At larger distances from the gene, the CCAT1 transcripts appeared spliced, implying that most CCAT1 transcripts undergo post-transcriptional splicing in the zone of the active gene. Finally, we show that unspliced CCAT1 transcripts can be detected in the cytoplasm during splicing inhibition, which suggests that there are several CCAT1 variants, spliced and unspliced, that the cell can recognize as suitable for export.

Asunto(s)

Cromatina , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Cromatina/metabolismo , Cromatina/genética , Cromatina/química , Empalme del ARN , Células HeLa , Hibridación Fluorescente in Situ

RESUMEN

In recent years, photovoltaic/thermal (PV/T) systems have played a crucial role in reducing energy consumption and environmental degradation, nonetheless, the low energy conversion efficiency presents a considerable obstacle for PV/T systems. Therefore, improving heat conversion efficiency is essential to enhance energy efficiency. In this paper, the PV/T system with the Tesla valve is proposed to solve this problem. Firstly, the cooling effect is simulated and analyzed in the system with four different flow channel structures: semicircle, rectangle, triangle and Tesla valve. The results indicate that the system with the Tesla valve exhibits superior cooling performance. Subsequently, several factors including angle, valve number, valve type, and pipe diameter ratio for the Tesla valve are further studied through numerical and simulation analysis. The results reveal that Tesla valves demonstrate optimal cooling performance when possessing the following structural parameters: complete symmetry, more valves, a 30-degree angle and a pipe diameter ratio of 1. Finally, four different types of fluid are selected to explore the Tesla valve. The conclusion shows that nanofluids with high density, low specific heat, and high thermal conductivity also improve the cooling performance. Thus, the PV/T system with the Tesla valve exhibits good heat dissipation and energy storage efficiency, electrical efficiency can reach 16.32% and thermal efficiency reach 59.65%.

RESUMEN

INTRODUCTION: The use of performance validity tests (PVTs) in a neuropsychological assessment to determine indications of invalid performance has been a common practice for over a decade. Most PVTs are memory-based; therefore, the Groningen Effort Test (GET), a non-memory-based PVT, has been developed. OBJECTIVES: This study aimed to validate the GET in patients with suspected chronic solvent-induced encephalopathy (CSE) using the criterion standard of 2PVTs. A second goal was to determine diagnostic accuracy for GET. METHOD: Sixty patients with suspected CSE referred for NPA were included. The GET was compared to the criterion standard of 2PVTs based on the Test of Memory Malingering and the Amsterdam Short Term Memory Test. RESULTS: The frequency of invalid performance using the GET was significantly higher compared to the criterion of 2PVTs (51.7% vs. 20.0% respectively; p < 0.001). For the GET index, the sensitivity was 75% and the specificity was 54%, with a Youden's Index of 27. CONCLUSION: The GET showed significantly more invalid performance compared to the 2PVTs criterion suggesting a high number of false positives. The general accepted minimum norm of specificity for PVTs of >90% was not met. Therefore, the GET is of limited use in clinical practice with suspected CSE patients.

RESUMEN

Background: Talaromyces marneffei (TM) is the third most prevalent opportunistic infection in HIV-positive patients after tuberculosis and cryptococcosis. However, such infection of non-HIV individuals has rarely been reported. Case Presentation: We describe a very rare case of a 52-year-old male who presented with a single space-occupying lesion on the right lung and was eventually diagnosed with pulmonary TM infection. The patient was HIV-negative and had liver cirrhosis with portal vein thrombosis. Lung tissue next-generation sequencing (NGS) revealed TM infection. We successfully treated the patient with voriconazole for 8 weeks and observed lesion absorption via subsequent CT. The patient consumed wild bamboo rats two months before admission. Mutations related to congenital immune deficiency were not detected by whole-exome sequencing. Conclusion: Early and timely diagnosis is critical for improving patient prognosis. NGS plays a vital role in the diagnosis of pulmonary TM infection in patients. To our knowledge, this is the first published case of pulmonary TM infection in an HIV-negative patient with liver cirrhosis.